Among malignant complications of HIV infection in sub-Saharan Africa, one of the most common cancers in the pre-ART era ? Kaposi?s sarcoma (KS) ? continues to be amongst the most common in the ART era. With continued incidence of KS in Africa comes both new questions and others that are still not yet resolved. In the last 4 years in Uganda and Kenya during the course of U54 CA190153, we have documented two disturbing (and related) findings: advanced stage of disease at time of KS diagnosis and poor survival. With recent ?Treat All? (for ART) and National Comprehensive Cancer Network (NCCN, for chemotherapy) guidelines now in place, will these outcomes change? A long-standing question is why does KS occur in HIV infection? Low CD4+ T cell count and high plasma HIV RNA are known determinants in untreated HIV infection, but these are neither necessary nor sufficient for KS. In the realm of diagnosis, delays in diagnosis have many manifestations. Thus, can KS diagnosis be more rapid? Finally, can simple interventions that help patients diagnosed with KS navigate to cancer care improve survival? Addressing each of the above questions has one common requirement ? swift access to patients recently diagnosed with KS. During the course of U54 CA190153, we implemented, to our knowledge, the first use of rapid case ascertainment (RCA) for cancer in Africa when we studied KS. RCA rapidly identifies persons recently diagnosed with a condition and performs detailed measurements prior to change in disease, death or loss to follow-up. Our overall objective in the current proposal is to use RCA to answer relevant clinical, epidemiologic and translational questions about KS in the ART era. Our Aims are to: Aim 1: Monitor critical epidemiologic parameters of KS in the ART era among HIV-infected adults in East Africa, specifically stage of disease at time of KS diagnosis and survival. Aim 2: Evaluate biologic determinants of incident KS in both ART-untreated HIV-infected patients as well as those with ART-mediated virologic suppression. Aim 3: Assess the predictive accuracy of digital photography of skin lesions, coupled with deep learning algorithms, to distinguish KS from non-KS mimickers. Aim 4: Determine the impact of ?patient navigation?, intended to enhance linkage to oncologic care in persons diagnosed with KS, on improving survival after KS diagnosis. To address these aims, we will leverage skin biopsy services in Uganda, Kenya and Tanzania and the field experience we have gained in U54 CA190153 to perform RCA on all patients with newly diagnosed KS as well as a well-conceived and novel ?test negative? control group. Findings will inform efforts aimed at controlling KS; improve our understanding of the pathogenesis of KS in the ART era; and evaluate novel strategies for KS diagnosis and linkage of patients newly diagnosed with KS to cancer care.